Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications

Jan 20, 2025Cardiovascular drugs and therapy

GLP-1 Receptor Activators as Treatments for Diabetes and Heart Disease: How They Work and What This Means for Patients

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

(GLP-1 RAs) have been shown to reduce the risk of (MACE) in diabetic patients.

GLP-1 RAs regulate insulin and glucagon secretion in pancreatic β-cells based on glucose levels.
These agents promote the proliferation of β-cells and inhibit their apoptosis.
GLP-1 RAs have demonstrated beneficial effects on cardiovascular health, including heart failure, hypertension, and ischemic cardiomyopathy.
The positive cardiovascular effects are associated with reduced inflammation, oxidative stress, and cell apoptosis.
The therapeutic potential of GLP-1 RAs is linked to their modulation of multiple cellular signaling pathways.

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BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a crucial incretin hormone secreted by intestinal endocrine L cells. Given its pivotal physiological role, researchers have developed (GLP-1 RAs) through structural modifications. These analogues display pharmacological effects similar to those of GLP-1 but with augmented stability and are regarded as an effective means of regulating blood glucose levels in clinical practice.

OBJECTIVE: This review aims to comprehensively summarize the role of GLP-1 RAs in the management of diabetes mellitus (DM) and cardiovascular disease (CVD), with a particular emphasis on the underlying signal transduction pathways and their therapeutic potential.

METHODS: A comprehensive review was carried out through literature research.

RESULTS AND DISCUSSION: In pancreatic β-cells, GLP-1 RAs regulate the secretion of insulin and glucagon in a glucosedependent manner by influencing signaling pathways such as cAMP, PI3K, and MAPK. They also contribute to the regulation of blood glucose levels by promoting the proliferation of β-cells and inhibiting apoptosis in these cells. Recent comprehensive studies have also demonstrated the favorable impact of GLP-1 RAs on cardiovascular wellbeing. In addition to the cardiovascular protection afforded by glucose metabolism regulation, a large body of evidence from animal and cellular studies has corroborated the beneficial effects of GLP-1 RAs on conditions such as heart failure (HF), hypertension, and ischemic cardiomyopathy. These benefits are mainly attributed to the alleviation of inflammatory responses, reduction of oxidative stress, and prevention of cell apoptosis. Clinical data shows that GLP-1 RAs can reduce the risk of (MACE) in diabetic patients.

CONCLUSION: GLP-1 RAs play an important role in the management of both diabetes and cardiovascular diseases. They show potential therapeutic value through the modulation of multiple signal transduction pathways. However, there may still be some issues in practical applications that require further research and resolution.

Key numbers

38%

Reduction in HF Hospitalization

Observed with tirzepatide in patients with heart failure with preserved ejection fraction.

2–3 min

Half-life of GLP-1

Native GLP-1's rapid degradation affects its clinical utility.

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Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications

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